Hereditary diffuse gastric cancer: What the clinician should know

Table 3 Comparison of hereditary cancer syndromes

Condition	Genetic pathology	Lifetime risk of gastric cancer	Histological subtype	Other clinical features
Hereditary diffuse gastric cancer	CDH1 germline and other gene mutations	80%	Diffuse	Association with lobular breast cancer and cleft-lip malformations
Lynch syndrome	Mutations in mismatch repair genes	4.8% in MLH1 carrier 9% in MLH2 carrier[58]	Mainly intestinal-type	Lifetime risk of colon cancer 31%-38%, endometrial cancer 34% and ovarian cancer 20%[59]
Familial adenomatous polyposis	APC germline mutations	Population risk[60]	No data	Malignant extraintestinal tumours rare < 3% (thyroid, pancreas, medulloblastoma)[61]
Li-Fraumeni syndrome	TP53 mutations	14.9%[62]	No predominant subtype	Associated with wide range of early-onset cancers. Includes haematological and solid organ cancers: sarcomas, breast, brain, adrenal and lung cancers
Peutz-Jegher’s syndrome	STK11 mutations	29%[63]	No data	Characteristic mucocutaneous pigmentation commonly around mouth and nose High cumulative lifetime risk of any cancer (85%), most commonly colorectal (50%)[58]
Juvenile polyposis syndrome	SMAD4 or BMPR1A mutations	121%[64]	No data	Also at increased

¹Frequency based on cross-sectional sample rather than lifetime risk from cohort study.